title: Breathing of awake goats during prolonged dysfunction of caudal M ventrolateral medullary neurons.
abstract: Cooling the caudal M ventrolateral medullary (VLM) surface for 30 s results in a sustained apnea in anesthetized goats but only a 30% decrease in breathing in awake goats. The purpose of the present study was to determine, in the awake state, the effect of prolonged (minutes, hours) caudal M neuronal dysfunction on eupneic breathing and CO2 sensitivity. Dysfunction was created by ejecting excitatory amino acid receptor antagonists or a neurotoxin on the VLM surface through guide tubes chronically implanted bilaterally on a 10- to 12-mm2 portion of the caudal M VLM surface of 12 goats. Unilateral and bilateral ejections (1 microliter) of selective antagonists for N-methyl-D-aspartic acid or non-N-methyl-D-aspartic acid receptors had no significant effect on eupneic breathing or CO2 sensitivity. Unilateral ejection of a nonselective excitatory amino acid receptor antagonist generally had no effect on eupneic breathing or CO2 sensitivity. However, bilateral ejection of this antagonist resulted in a significant 2-Torr hypoventilation during eupnea and a significant reduction in CO2 sensitivity to 60 +/- 9% of control. Unilateral ejection of the neurotoxin kainic acid initially stimulated breathing; however, breathing then returned to near control with no incidence of apnea. After the kainic acid ejection, CO2 sensitivity was reduced significantly to 60 +/- 7% of control. We conclude that in the awake state a prolonged dysfunction of caudal M VLM neurons results in compensation by other mechanisms (e.g., carotid chemoreceptors, wakefulness) to maintain near-normal eupneic breathing, but compensation is more limited for maintaining CO2 sensitivity.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, USA.
authors.forename: H V
authors.initials: HV
authors.lastname: Forster
authors.forename: L G
authors.initials: LG
authors.lastname: Pan
authors.forename: T F
authors.initials: TF
authors.lastname: Lowry
authors.forename: T
authors.initials: T
authors.lastname: Feroah
authors.forename: W M
authors.initials: WM
authors.lastname: Gershan
authors.forename: A A
authors.initials: AA
authors.lastname: Whaley
authors.forename: M M
authors.initials: MM
authors.lastname: Forster
authors.forename: B
authors.initials: B
authors.lastname: Sprtel
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D003080:Cold Temperature; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006041:Goats; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D002245:Carbon Dioxide; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid